The concerns of skin aging are of increasing importance to the fields of dermatology and cosmetic medicine. Skin aging is a complicated process caused in part by the reduction of Extracellular Matrix (ECM) components including collagen, elastin and fibronectin (Callaghan, T M and Wilhelm, K P (2008) Int J. Cosmet. Sci. 30:313-322). Type I collagen is the most abundant type of collagen and functions in structural integrity, cell adhesion and migration, tissue remodeling and wound healing (Trojanowska, M et al., (1998) J. Mol. Med. 76:266-267; Chiquet, M. et al., (1996) Biochem. Cell Biol. 74:737-744). In 1993 a pentapeptide (Lys-Thr-Thr-Lys-Ser also known as KTTKS SEQ ID NO: 1)) derived from the carboxyl-terminus of type I procollagen was shown to promote ECM production (Katayama, K et al., (1993) J. Biol. Chem. 268:9941-9944). In an in vitro model using human lung fibroblasts, the pentapeptide was found to significantly augment the ECM proteins through increased synthesis of collagen types I and III and fibronectin.
Although the aforementioned in vitro data demonstrated the pentapeptide's ability to stimulate collagen and fibronectin synthesis, its net charge posed a challenge to transcutaneous penetration. In order to enhance the peptides activity, stability and increase lipophilicity, Lintner et al. (Lintner (2003) U.S. Pat. No. 6,620,419) conjugated the pentapeptide to the 16-carbon fatty acid, palmitate, to create Palmitoyl KTTKS (Pal-KTTKS, SEQ ID NO: 2). This fatty acid modification resulted in more effective delivery across skin relative to KTTKS (SEQ ID NO: 1) alone (Lintner, K (2002) Ann Dermatol Venereol 129: 1S 105; Mas-Chamberlin, C et al., (2002) Ann Dermatol Venereol 129: 1S 456; Tsai, T C and Hantash, B M (2008) Clin Med 2:1-20). Palmitoyl-KTTKS (SEQ ID NO: 2) was one of the first oligopeptides to be developed as a cosmetic agent and is currently the active ingredient in the cosmetic agent Matrixyl™ (Sederma SAS). The Pal-KTTKS (SEQ ID NO: 2) has been formulated with a skin care active and a dermatologically acceptable carrier to form skin care compositions for topical treatment of skin (The Proctor and Gamble Company). The resulting compositions have been found to be advantageous for skin treatment particularly against the formation of wrinkles and against other skin aging effects (Robinson (2002) U.S. Pat. No. 6,492,326). The Pal-KTTKS (SEQ ID NO: 2) has been found to decrease fibroblast cell viability under certain conditions.
It is desirable to provide alternative oliogopeptides capable of promoting ECM protein production and secretion from fibroblasts.